Amyloid plaque refers to abnormal protein deposits that accumulate in the brain. These deposits are a characteristic feature observed in the brains of individuals with certain neurodegenerative conditions.
Composition and Formation
Amyloid plaques are primarily composed of misfolded fragments of a protein called amyloid-beta (Aβ). This Aβ protein is generated from a larger parent protein known as amyloid precursor protein (APP). APP is a transmembrane protein particularly abundant in neurons.
The formation of Aβ peptides begins with the cleavage of APP by two enzymes: beta-secretase and gamma-secretase. The Aβ42 isoform is particularly prone to aggregation due to its “stickier” chemical nature.
Aβ peptides aggregate, first forming small, soluble clusters called oligomers, which are considered highly toxic. These oligomers then assemble into insoluble fibrils. These fibrils accumulate outside neurons, forming dense, extracellular amyloid plaques.
Impact on Brain Function
The accumulation of amyloid plaques in the brain can disrupt normal brain function through several mechanisms. These plaques can interfere with synaptic communication, which is the process by which neurons transmit signals to each other. This disruption can impair the brain’s ability to process and transmit information effectively.
Beyond direct interference, amyloid plaques can trigger an inflammatory response in the brain, a process known as neuroinflammation. This inflammatory state involves the activation of immune cells like microglia and astrocytes, which can release pro-inflammatory substances. Such persistent inflammation contributes to neuronal damage and dysfunction.
Amyloid plaques also contribute to oxidative stress within brain cells. Oxidative stress results from an imbalance between the production of reactive oxygen species and the body’s ability to detoxify them, leading to cellular damage. These combined effects of disrupted communication, inflammation, and oxidative stress can ultimately lead to the dysfunction and eventual death of neurons.
Association with Alzheimer’s Disease
Amyloid plaques are a hallmark pathological feature found in the brains of individuals with Alzheimer’s disease (AD). Their presence, along with neurofibrillary tangles composed of tau protein, is required for a neuropathological diagnosis of AD. These plaques are thought to accumulate in the brain years before the onset of AD symptoms.
The “amyloid cascade hypothesis” posits that the accumulation of Aβ peptides is an early event in AD, initiating a sequence of pathological changes. This hypothesis suggests that Aβ aggregation leads to the formation of plaques, which then trigger the abnormal phosphorylation and aggregation of tau protein into neurofibrillary tangles. Both plaques and tangles contribute to neuronal damage and cognitive decline.
While strongly associated with AD, the exact causal relationship between plaques and the full progression of the disease remains a complex area of ongoing research. Plaques often coexist with other brain abnormalities in AD, such as neurofibrillary tangles, and these different pathologies can interact to influence disease development. Recent therapeutic approaches targeting amyloid-beta protofibrils provide further support for the amyloid hypothesis.